Arsenic (As) from drinking water is a major public health problem affecting over 200 million people around the world. Epidemiologic research, including our own, has demonstrated associations of As with non- malignant respiratory outcomes including impaired lung function and also with pulmonary infections. While the physiological mechanisms by which As induces non-malignant lung diseases remain largely unknown, emerging evidence from animal studies suggests disruption of the immune system as a plausible mode of action. The role of As on immune mechanisms underlying respiratory dysfunction has not been evaluated in humans. In this study, we propose to examine effects of long term As exposure from drinking water on respiratory outcomes and related immune function by measuring pulmonary function tests and activated T-cell function in 630 well-characterized adults in the HEALS cohort. Additionally, we will explore a possible protective role of vitamin D, an immune modulator, on lung function in the same population. By design, we carefully selected the following three groups of individuals (210 in each) from our population cohort based on their water and urinary As levels measured at baseline in 2000 and at three follow- up visits over 3-10 years. Group 1 includes subjects consistently exposed to low water As (<10g/L) since baseline; Group 2 includes subjects exposed to high levels of water As (>50g/L) at baseline who then switched to low water As; and Group 3 includes subjects consistently exposed to high water As. We will compare the study outcomes (lung function and T-cell function) across groups 1, 2 and 3 and evaluate trends across these groups. We will consider water As, urinary As and urinary As metabolites as markers of As exposure. We will also construct a Cumulative Arsenic Index (CAI) as a measure of As exposure. Findings from this highly feasible and cost-efficient study will be able to provide important data, for the first time, from a prospective population-based study on pulmonary and immune effects of low-to-moderate doses of As exposure.